Primary CD8+ cells from HIV-infected individuals can suppress productive infection of macrophages independent of beta-chemokines.
The productive infection of human monocyte-derived macrophages (Mphi) by HIV was suppressed by primary CD8+ cells from asymptomatic HIV-infected individuals. This anti-HIV response was noncytotoxic; removal of the CD8+ cells from the infected Mphi leads to virus production. CD8+ cells inhibited HIV replication when separated from the infected Mphi by a transwell filter insert, indicating a diffusible factor made by the CD8+ cells suppressed productive infection of Mphi. Three beta-chemokines, which can be secreted by activated CD8+ cells, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1alpha and MIP-1beta prevented HIV replication in the Mphi cultures. In addition, incubation of acutely infected Mphi with a mixture of neutralizing antibodies to RANTES, MIP-1alpha, and MIP-1beta enhanced virus replication. Nevertheless, neutralization of beta-chemokines with specific antibodies did not abolish the suppression by CD8+ cells of HIV replication in Mphi. Thus, even though beta-chemokines decrease HIV replication in Mphi, these cytokines are not responsible for the ability of CD8+ cells to inhibit HIV production in these cells.
Barker
E
E
Department of Medicine, University of California, San Francisco, CA 94143-1270, USA.
Bossart
K N
KN
Levy
J A
JA
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000502:physiology; D019742:Chemokines, CC / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D008264:Macrophages / Q000821:virology*; D014779:Virus Replication
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins